This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Project 3: MATERNAL CONSUMPTION OF A WESTERN DIET PROMOTES OBESITY AND HYPERTENSION IN OFFSPRING PI Kevin Pearson PROJECT DESCRIPTION: The intrauterine environment affects the development of the growing embryo and an unsuitable environment can lead to termination of pregnancy. However, emerging research has shown that more subtle factors can potentially influence long-term health in the offspring. For instance, malnourished pregnant mothers produce smaller offspring that have a higher incidence of obesity, diabetes, and heart disease during adulthood. However, in the Western world, maternal obesity is an ever-increasing problem and epidemiology studies are now pointing to metabolic derangements in their offspring. Taking these findings into consideration, the general hypothesis of this proposal is maternal consumption of a Western (high fat) diet during pregnancy and nursing will promote obesity and hypertension in offspring through activation of the renin-angiotensin system, and maternal consumption of resveratrol will block the negative effects. The goal is to gain detailed insights into the effects of pre-weaning environmental changes caused by unhealthy diets, or the presence of resveratrol, on obesity and cardiovascular disease in mice. For this purpose we will manipulate the dietary composition of female mice six weeks prior to mating (or at mating), throughout pregnancy, and until 14 days after giving birth. Offspring from mothers in all groups will then be fed a normal, low-fat diet after weaning. Obesity, glucose and insulin tolerance, and hypertension will be monitored in the offspring. Obesity, diabetes, and cardiovascular disease are at epidemic levels and interventions targeting gestation might be an efficient way to stem the tide.